Successful development of a vaccine against HIV will require the induction of neutralizing antibody sufficient to prevent infection. Recent work analyzing HIV specific antibody responses from infected individuals has shown that broadly neutralizing antibodies are directed at several sites on the HIV Env. Moreover, several of these antibodies have unique characteristics such as a high rate of somatic mutation and/or long CDRH3 regions. Thus, improving antigen design and understanding the in vivo mechanisms that control the maturation of the B cell response with various vaccines should facilitate development of a successful HIV vaccine. The data obtained over this past year have shown the following; 1. Performed gene profiling of NHP that had been immunized with multiple different adjuvants with HIV env protein to determine the innate mechanisms which controlled antibody and CD4 T cell responses. A set of gene signatures was also shown to correlate with qualitative measures of antibody production including ADCC, Fc binding and patterns of glycosylation. 2. Adjuvant Development: Using novel synthetic polymers that could form particles in vivo in response to temperature or next generation polymers that can accommodate up to 128 attachment sites, studies were initiated to assess how HIV peptides and glycan peptides could be formulated to induced focused antibody responses to neutralizing sites on the HIV envelope. Agonists which activate toll like receptor 7 and 8 ligands were used to combine with these polymer-Env immunogens in mouse and NHP studies.